Transcriptome analysis reveals distinct patterns of long noncoding RNAs in heart and plasma of mice with heart failure.

Transcriptome analysis reveals distinct patterns of long noncoding RNAs in heart and plasma of mice with heart failure.
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转录组分析揭示心力衰竭小鼠心脏和血浆中长非编码 RNA 的独特模式

DOI:
10.1371/journal.pone.0077938
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Geng B
Geng B
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Li D;Chen G;Yang J;Fan X;Gong Y;Xu G;Cui Q;Geng B

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目的探讨心力衰竭(HF)时心脏组织、全血和血浆中长非编码RNA(LncRNAs)转录组的整体变化和特点及其与成对编码基因表达的关系。方法采用基因芯片技术检测心力衰竭时小鼠心脏、全血和血浆中转录水平下调的lncRNAs的转录水平。我们用定量聚合酶链式反应证实了lncRNAs的变化。结果我们发现并证实了在心力衰竭过程中存在大量非调控的lncRNAs,提示了lncRNAs在心力衰竭中的潜在作用。值得注意的是,在HF期间,LncRNA在血浆和其他组织中的表达模式不同。LncRNA表达与LncRNA长度呈正相关,而血浆中LncRNA表达与LncRNA长度无相关性,提示血浆LncRNA表达与LncRNA长度的整体相关性可能是心衰的生物标志物。总共有32个lncRNAs在心脏、全血和血浆中均有表达,提示它们可能是心力衰竭的生物标志物。此外,正义重叠的LncRNAs倾向于与其编码基因对的表达一致,而反义重叠的LncRNAs则倾向于在血浆中表现出相反的表达,因此不同类型的LncRNAs在HF中可能具有不同的特征。有趣的是,我们揭示了血浆和心脏中lncRNAs表达变化之间的负相关关系,因此循环中lncRNAs的水平可能不仅代表心力衰竭心脏的被动渗漏,而且还代表心力衰竭期间循环细胞或其他细胞的主动调节或释放。结论在心力衰竭过程中,我们发现血浆中有稳定的lncRNAs表达,这可能是血浆中的一种新的成分。循环中lncRNAs在心力衰竭过程中的不同表达模式表明,lncRNAs可能对应激做出积极反应,从而成为心力衰竭诊断和治疗的生物标志物。
Objective To assess the global changes in and characteristics of the transcriptome of long noncoding RNAs (LncRNAs) in heart tissue, whole blood and plasma during heart failure (HF) and association with expression of paired coding genes. Methods Here we used microarray assay to examine the transcriptome of LncRNAs deregulated in the heart, whole blood, and plasma during HF in mice. We confirmed the changes in LncRNAs by quantitative PCR. Results We revealed and confirmed a number of LncRNAs that were deregulated during HF, which suggests a potential role of LncRNAs in HF. Strikingly, the patterns of expression of LncRNA differed between plasma and other tissue during HF. LncRNA expression was associated with LncRNA length in all samples but not in plasma during HF, which suggests that the global association of LncRNA expression and LncRNA length in plasma could be biomarkers for HF. In total, 32 LncRNAs all expressed in the heart, whole blood and plasma showed changed expression with HF, so they may be biomarkers in HF. In addition, sense-overlapped LncRNAs tended to show consistent expression with their paired coding genes, whereas antisense-overlapped LncRNAs tended to show the opposite expression in plasma; so different types of LncRNAs may have different characteristics in HF. Interestingly, we revealed an inverse correlation between changes in expression of LncRNAs in plasma and in heart, so circulating levels of LncRNAs may not represent just passive leakage from the HF heart but also active regulation or release of circulatory cells or other cells during HF. Conclusions We reveal stable expression of LncRNAs in plasma during HF, which suggests a newly described component in plasma. The distinct expression patterns of circulatory LncRNAs during HF indicate that LncRNAs may actively respond to stress and thus serve as biomarkers of HF diagnosis and treatment.
DOI: 10.1186/1756-9966-27-19
发表时间: 2008-07-16
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影响因子: --
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